Cl-amidine hydrochloride is an orally available PAD inhibitor that blocks histone 3 deimination and neutrophil extracellular trap formation and improves survival in septic mice. It induces apoptosis in cancer cells and induces miR-16 to cause cell cycle arrest.

PAD4:5.9 μM

METHODS: Mouse primary splenocytes were treated with 1 μg/mL LPS and 10 μM Cl-amidine. Cell culture supernatants were collected 6 hours after treatment. TNF-α and pro-inflammatory properties of plasma and cell culture supernatants were determined by ELISA. Cytokine expression.
RESULTS Cl-amidine decreased the concentration of TNF-α in plasma. At the same time, Cl-amidine treatment could significantly reduce the concentrations of these pro-inflammatory cytokines (IL-1β, IL-6). [1]
METHODS: HT29 and TK6 cells were treated with Cl-amidine (0, 5, 10, 15, 25, 50 μg/mL, 24 hours) to detect whether Cl-amidine could induce apoptosis of HT29 and TK6 cells.
RESULTS Cl-amidine induced apoptosis of these cells in a dose-dependent manner. [2]

METHODS: Cl-amidine (40 mg/kg) was administered intraperitoneally to mice 1 hour after cecal ligation and puncture (CLP) to observe the effect of Cl-amidine on protecting mice from sepsis-induced lethality. RESULTS Cl-amidine protected mice from sepsis-induced lethality, and Cl-amidine-treated CLP animals had a higher long-term survival rate. [1]